This application requests funding for the TNPRC for the five-year period beginning May 1, 2003 through April 30, 2008. Funds will be used to support the administration, operations, veterinary resources, and scientific research resources of the Center. Additional funds to support pilot research projects and colony-health-related research resource projects are also requested. The research program at the TNPRC has been focused on infectious disease research for close to three decades. Although the majority of the Center's research efforts are devoted to infectious disease, there are also rapidly expanding programs in gene therapy and assisted reproductive technologies (ART). The infectious disease program currently focuses on AIDS, Malaria Microsporidial diseases, and Lyme disease. These are multidisciplinary studies involving investigators in numerous Divisions at the TNPRC as well as collaborators outside the Center. The studies cover the spectrum from transmission, diagnosis and pathogenesis, development of vaccine strategies and chemotherapeutic treatments, and pathologic lesions to gene sequences. In addition, the development of the gene therapy program allows for novel approaches to the treatment of many types of disease and preclinical modeling of a variety of gene therapy modalities. The last five years, and particularly the last year, have seen significant changes at the Center, following the retirement of Dr. Peter Gerone and the naming of Dr. Andrew Lackner as the new Director. Since October 1, 2001 when Dr. Lackner became Director, leadership in several of the Divisions has changed, new Divisions have been formed, and the business office (now Administrative Services) has begun reorganization. The result is a Center that now places more emphasis on research programs and which has experienced a 50% growth in its grant portfolio. These changes have been facilitated by a very helpful and collegial host institution. The new organizational structure and leadership team at the TNPRC and recent successes in obtaining grant funding and attracting outside collaboration suggest that the Center is poised for a period of significant growth and improvement.